Angiotensin-(1-7) Attenuates Angiotensin Ⅱ-induced Connexin Remodeling Associated With SHP-1

Objective: To investigate whether angiotensin 1-7 [Ang-(1-7)] inhibits angiotensin II(AngⅡ)-induced c-Src activation via SHP-1,thereby improving Cx43 expression and function.Methods: HL-1 cells were divided into five treatment groups:Control,AngⅡ,AngⅡ+SU6656(a specific c-Src inhibitor),AngⅡ+Ang-(1-7),AngⅡ+Ang-(1-7)+SSG(a specific SHP-1 inhibitor).Western blot was used to detect the expression of Cx43,p-c-Src,SHP-1.Cell immunofluorescence and scrape-loading and dye transfer(SLDT)were used to observe the spatial distribution of Cx43 and the function of gap junctions.Results: Compared with control group,higher concentration of AngⅡ increased the c-Src expression,but inhibited the expression of Cx43 and shortened the gap connection conduction distance.Compared with AngⅡ group,AngⅡ+Ang-(1-7)and AngⅡ+SU5565 effectively increased Cx43 expression,accompanying by down-regulation of p-c-Src.Moreover,with the increasing expression of Cx43,the transmembrane transport efficiency of gap junctions was promoted.Compared with AngⅡ +Ang-(1-7)group,AngⅡ +Ang-(1-7)+SSG effectively inhibited SHP-1 expression,which led to the down-regulation of Cx43 and the gap junction conduction distance shortened,but increased the epxression of c-Src.Conclusion: These results suggest that Ang-(1-7)inhibits c-Src activity by increasing the expression of SHP-1,thereby exerting an antagonistic effect on AngⅡ,leading to increased Cx43 expression and improved gap junction function.